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Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...

Positive Regulator Molecules

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.

Positive Regulator Molecules

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.

Delivery Pathways to the Lysosome

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...

Regulated Protein Degradation

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...

Regulated Protein Degradation

Regulated Protein Degradation

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Related Experiment Video

Updated: Dec 15, 2025

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

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CDK4/6 regulate lysosome biogenesis through TFEB/TFE3.

Qiuyuan Yin¹, Youli Jian², Meng Xu²

¹State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan and Center for Life Science, School of Life Sciences, Yunnan University, Kunming, China.

The Journal of Cell Biology

|July 15, 2020

Summary

This summary is machine-generated.

Cyclin-dependent kinases CDK4/6 control lysosome numbers during cell division by regulating TFEB/TFE3 activity. Inhibiting CDK4/6 boosts lysosome biogenesis, impacting cancer and lysosomal disorder therapies.

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Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

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Published on: October 18, 2024

Area of Science:

Cell Biology
Molecular Biology
Biochemistry

Background:

Lysosomes are crucial organelles for cellular degradation and signaling.
Lysosome biogenesis adapts to cellular needs, but its regulation during the cell cycle remains unclear.
Understanding cell cycle-dependent lysosome regulation is vital for cellular homeostasis.

Purpose of the Study:

To investigate the role of cyclin-dependent kinases CDK4/6 in regulating lysosome biogenesis during the cell cycle.
To identify the molecular mechanisms by which CDK4/6 influence lysosome numbers.
To explore the therapeutic potential of targeting this pathway in diseases.

Main Methods:

Utilized chemical and genetic inactivation of CDK4/6.
Investigated the interaction and phosphorylation of transcription factors TFEB and TFE3 by CDK4/6.
Analyzed lysosomal numbers and TFEB/TFE3 localization during different cell cycle phases.

Main Results:

CDK4/6 inactivation led to increased lysosomal numbers.
CDK4/6 were found to interact with and phosphorylate TFEB/TFE3 in the nucleus, promoting their cytoplasmic shuttling.
Lysosome numbers increased during S and G2/M phases, correlating with diminished CDK4/6 activity due to cyclin D turnover.
Discovered a novel mechanism controlling TFEB/TFE3 nuclear export and lysosome biogenesis.

Conclusions:

CDK4/6 are key regulators of lysosome biogenesis in the cell cycle.
The CDK4/6-TFEB/TFE3 axis provides a molecular link between cell cycle progression and lysosome adaptation.
CDK4/6 inhibitors enhance autophagy and lysosome-dependent degradation, suggesting therapeutic applications for cancer and lysosomal disorders.